Flashcards in Proteoglycans Deck (19)
Where are proteoglycans found?
both on the outside surface of cells and in the ECM
What are the components of proteoglycans?
a core protein and a GAG composed of repeating disaccarhides of amino and acid sugars
How do proteoglycans form hydrated gels?
a core protein is COVALENTLY attached to many negatively charged GAGs (in 3D), which can bind water and sodium to withstand compressive forces. Compressive forces will force the water but the polyanion nature of the GAGs will cause water to be resorbed again
T or F. GAGs take up a large space relative to their mass. Why or why not?
T. Because its a very hydrated gel and have an inflexible nature
How do proteoglycans interact with matrix proteins?
the negative nature of GAGs allows them to bind to positive proteins in the matrix (like collagen) via a BBXB sequence on the proteins (B= basic AA, lysine or arginine; X= any AA)
Thus, these are IONIC interactions, not covalent
How are GAGs linked to core proteins in proteoglycans?
O-linked glycosylated chains through a serine on the core protein
What is the typical composition of GAGs?
Disaccharides of amino (which can be sulfated- adds negative charges- or acetylated) and acid sugars (which have carboxylic acid on them) that repeat a lot and a link TAG (xyl-gal-gal)
Can a single core protein have different types of proteoglycans attached to it?
Yes. However, once a proteoglycan is made, it is always composed of repeating groups of the same disaccharides
What is unique about hyaluronate?
it is a free GAG, thus it is not attached to a core protein and is not sulfated. Forms the core of Aggrecan in which a link protein attached proteoglycan core proteins. Secreted through a different secretory pathway too
Where is hyaluronate found?
cartilage, synovial fluid, and vitreous humor
How are GAGs like chondroitin sulfate, dermatan sulfate, heparin, and heparin sulfate attached to core proteins?
they do not exist as free GAG like hyaluronate but are COVALENTLY attached to core proteins via a hydroxylated serine AA (O-linked) on the protein and a link trisaccharide, consisting of xyl-gal-gal
These are sulfated (adds another negative charge) and are found many places
Heparin is an anticoagulant (see coagulation lecture) but also competes for binding with LPL so LPL levels can be assayed by administering a shot of heparin
What sequence is needed on the core protein to bind the link trisaccharide?
Asp/Glu-X-**Ser**-Gly. Link trisaccharide attaches to the serine. Sulfating of the GAG is the last step (in some), and is achieved via sulfate transfer from PAPS (made by ATP)
The synthesis of all these steps use UDP activated heads (except the PAPS step)
How is Aggrecan formed?
proteoglycans attach to the sides of a hyaluronate acid molecule via **link proteins**
What other things can proteoglycans do?
they can serve as a reserve depot for growth factors (i.e. fibroblast growth factor) and can bind to fibronectin to aid in cell-stability/adhesion
How can proteoglycans be incorporated on the cell surface?
they can be part of integral proteins, bound to the surface via inositol, or via interaction with an integrally bound proteoglycan
How are proteoglycans degraded?
GAGs are usually transported to endosomes for degradation and the core proteins are sometimes recycled
Deficiency in proteoglycan degradation (particularly GAG breakdown) can lead to what?
muccopolysaccharidoses (i.e. Hunter disease, San-Filipo, Hurler syndrome (iduronidase deficiency))
What is lupus?
auto-immune disease causing loss of cartilage